The overall objectives of this research project are: (1) determination of the cell type which expresses the Ir-1 gene product; (2) genetic mapping of immune response genes with respect to the H-2 locus; (3) attempts to characterize and isolate the Ir-1 gene product; (4) search for histocompatibility-linked immune response genes associated with susceptibility or resistance to infectious, neoplastic, and autoimmune diseases. For the study of these four problems, the following experimental approaches are used: (1) The analysis of the production of nonresponder allotype antibody in tetraparental mice, produced from either histocompatible high and low responder parents, or from histoincompatible low responder parents, to probe the possible role of allogeneic effect in this system. The study of antigen binding lymphocytes for (T,G)-A--L, with autoradiography, with special attention to the binding characteristics of T and B cells, and the inhibition of this binding by anti-H-2 and anti-Ir-1 sera. Application of the T-cell dependent lymphocyte transformation test (3H-thymidine uptake) in cell culture for (T,G)-A--L, (H,G)-A--L, and Phe,G)-A--L. (2) Mapping studies on natural antigens such as ovomucoid and BGG, and on synthetic antigens of specified sequence. The latter will be used to elucidate the structure of the antigenic determinant recognized in Ir-1 regulated immune reactions. Our mapping studies are continuously extended to new recombinants in the Ir and/or MLC region. (3) Production of alloantisera across Ir differences in H-2-similar recombinant mice. These are studied in respect to the cellular distribution, function, and position of the Ir-1 gene product. (4) We are developing systems for the study of Rgv-1, and H-2-linked murine virus-leukemia resistance gene, and its relationship to the Ir-1-type immune response genes. Cooperative studies on the immunogenetic regulation of murine lymphocytic choriomeningitis, and ectromelia in mice, and of SLE in humans are in progress.